1. Field of the Invention
This invention generally relates to chemicals that bind to receptors in the TRP (transient receptor potential) ion channel family, more particularly to the subgroup of long TRP (or TRPM) channels, and most particularly to those that specifically bind to the TRP channel called “trp-p-8” (or TRP-M8); TRP-M8 receptors being present at elevated levels in certain cancers, such as prostate cancer. This invention more particularly relates to compositions containing radioactive phosphorus (32P or 33P) within the molecular structure, said compositions which are useful, for example, in radioreceptor applications.
2. Description of Related Art
Laus et al. (Prostate tumor polynucleotide compositions and methods of detection thereof) in U.S. Pat. No. 6,194,152, issued Feb. 27, 2001, herein incorporated by reference, described a novel polynucleotide and the polypeptide encoded by it, that was detected exclusively in human prostate tumor cells, but not in non-malignant tissues such as the brain, visceral organs, or glands. The mRNA for the synthesis of this specific protein was also detected in samples of malignant mammary gland, melanoma, and colorectal cancer cells. The 1044 amino acid protein, deciphered from the cDNA sequence, was named trp-p-8 because of its structural homology to receptors of the transient receptor potential (TRP) family. A paper describing this gene/protein was published in Cancer Research (vol. 61 pg. 3760-3769, May 1, 2001. L. Tsavaler, M. H. Shapero, S. Morkowski, and R. Laus: “Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins.”)
The trp-p-8 is preferably named TRP-M8 because of its structural homology to other protein receptors in this family. The identifying tags for the sequences in the NicePro TrEMBL Database are Q8R405 (mouse TRP-M8) Q8R444 (rat TRP-M8 or CMR1) and Q8TAC3 (human TRP-M8, or trp-p-8).
Prostate cancer is the most common cancer among men in the United States. Despite the fact that this cancer was diagnosed in almost 200,000 U.S. men in the year 2002 (and will lead to the death of over 30,000 men), there is no universally agreed-upon strategic plan for its diagnosis and management. Brachytherapy, a treatment well known in the art, involves the implantation of radioactive seeds directly into the prostate gland. The radioactive seeds used in brachytherapy may include iodine-131, palladium, radium, iridium, cesium, or phosphorus.
In the past, various radioactive phosphorus compounds have been used clinically in some oncological applications, for example for the treatment of ovarian cancer, leukemia, and for treating polycythemia rubra vera (uncontrolled proliferation of red blood cells). Their use, however, suffers from the inability to precisely target the malignant cells, which subjects the patient to potentially severe toxic side effects. More specific radioisotopes are needed that directly target malignant tissue and cells to improve diagnosis and treatment of certain cancers. Such radioisotopes are disclosed herein.